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HelpTest ID: UCDP Urea Cycle Disorders Gene Panel, Varies
Ordering Guidance
The recommended first-tier biochemical tests to screen for urea cycle disorders are a combination of quantitative plasma amino acids and urinary orotic acid. Order AAQP / Amino Acids, Quantitative, Plasma and OROT / Orotic Acid, Random, Urine.
Customization of this panel and single gene analysis for any gene present on this panel is available. For more information see CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies.
Targeted testing for familial variants (also called site-specific or known mutations testing) is available for the genes on this panel. See FMTT / Familial Variant, Targeted Testing, Varies. To obtain more information about this testing option, call 800-533-1710.
Shipping Instructions
Specimen preferred to arrive within 96 hours of collection.
Specimen Required
Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. For instructions for testing patients who have received a bone marrow transplant, call 800-533-1710.
Submit only 1 of the following specimens:
Specimen Type: Whole blood
Container/Tube: Lavender top (EDTA) or yellow top (ACD)
Specimen Volume: 3 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send whole blood specimen in original tube. Do not aliquot.
Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated 14 days
Specimen Type: Skin biopsy
Supplies: Fibroblast Biopsy Transport Media (T115)
Container/Tube: Sterile container with any standard cell culture media (eg, minimal essential media, RPMI 1640). The solution should be supplemented with 1% penicillin and streptomycin (Eagle's minimum essential medium with 1% penicillin and streptomycin).
Specimen Volume: 4-mm punch
Specimen Stability Information: Refrigerated (preferred)/Ambient
Additional Information: A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks is required to culture fibroblasts before genetic testing can occur.
Specimen Type: Cultured fibroblast
Container/Tube: T-25 flask
Specimen Volume: 2 Flasks
Collection Instructions: Submit confluent cultured fibroblast cells from a skin biopsy from another laboratory. Cultured cells from a prenatal specimen will not be accepted.
Specimen Stability Information: Ambient (preferred)/Refrigerated (<24 hours)
Additional Information: A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks is required to culture fibroblasts before genetic testing can occur.
Specimen Type: Blood spot
Supplies: Card-Blood Spot Collection (Filter Paper) (T493)
Container/Tube:
Preferred: Collection card (Whatman Protein Saver 903 Paper)
Acceptable: PerkinElmer 226 (formerly Ahlstrom 226) filter paper, or blood spot collection card
Specimen Volume: 5 Blood spots
Collection Instructions:
1. An alternative blood collection option for a patient older than 1 year is a fingerstick. For detailed instructions, see How to Collect Dried Blood Spot Samples.
2. Let blood dry on the filter paper at ambient temperature in a horizontal position for a minimum of 3 hours.
3. Do not expose specimen to heat or direct sunlight.
4. Do not stack wet specimens.
5. Keep specimen dry.
Specimen Stability Information: Ambient (preferred)/Refrigerated
Additional Information:
1. Due to lower concentration of DNA yielded from blood spot, it is possible that additional specimen may be required to complete testing.
2. For collection instructions, see Blood Spot Collection Instructions.
3. For collection instructions in Spanish, see Blood Spot Collection Card-Spanish Instructions (T777).
4. For collection instructions in Chinese, see Blood Spot Collection Card-Chinese Instructions (T800).
Specimen Type: Saliva
Patient Preparation: Patient should not eat, drink, smoke, or chew gum 30 minutes prior to collection.
Supplies: Saliva Swab Collection Kit (T786)
Specimen Volume: 1 Swab
Collection Instructions: Collect and send specimen per kit instructions.
Specimen Stability Information: Ambient 30 days
Additional Information: Due to lower concentration of DNA yielded from saliva, it is possible that additional specimen may be required to complete testing.
Forms
1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available:
-Informed Consent for Genetic Testing (T576)
-Informed Consent for Genetic Testing (Spanish) (T826)
2. Molecular Genetics: Biochemical Disorders Patient Information (T527)
3. If not ordering electronically, complete, print, and send a Biochemical Genetics Test Request (T798) with the specimen.
Useful For
Follow up for abnormal biochemical results suggestive of a urea cycle disorder (UCD)
Establishing a molecular diagnosis for patients with a UCD
Identifying variants within genes known to be associated with UCD, allowing for predictive testing of at-risk family members
Genetics Test Information
This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in 16 genes associated with urea cycle disorders (UCD). This test includes next-generation sequencing to test for variants in the genes indicated: ALDH18A1, ARG1, ARG2, ASL, ASS1, CA5A, CPS1, GLUD1, GLUL, NAGS, OAT, OTC, SLC25A13, SLC25A15, SLC7A7, and UMPS. See Targeted Genes and Methodology Details for Urea Cycle Disorders Gene Panel and Method Description for additional details.
Identification of a disease-causing variant may assist with diagnosis, prognosis, clinical management, familial screening, and genetic counseling for UCD.
Method Name
Sequence Capture and Targeted Next-Generation Sequencing (NGS) followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing
Reporting Name
Urea Cycle Disorders Gene PanelSpecimen Type
VariesSpecimen Minimum Volume
See Specimen Required
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Varies | Varies | ||
Clinical Information
Urea cycle disorders (UCD) are a group of inherited disorders of nitrogen detoxification that result when any of the enzymes in the urea cycle have reduced or absent activity. These disorders include carbamoylphosphate synthetase I deficiency, ornithine transcarbamylase (OTC) deficiency, argininosuccinic acid synthetase deficiency (citrullinemia), argininosuccinic acid lyase deficiency (argininosuccinic aciduria), arginase deficiency, the cofactor producer, N-acetyl glutamate synthetase (NAGS) deficiency, and two amino acid transporters, ornithine translocase deficiency (hyperornithinemia, hyperammonemia, homocitrullinuria syndrome) and citrin deficiency. The role of the urea cycle is to metabolize and clear waste nitrogen, and defects in any of the steps of the pathway can result in an accumulation of toxic ammonia in the nervous system. The urea cycle is also responsible for endogenous production of the amino acids citrulline, ornithine, and arginine.
Infants with a complete urea cycle enzyme deficiency typically appear normal at birth, but they present in the neonatal period with lethargy, seizures, hyper- or hypoventilation, and ultimately coma or death, as a result of elevated ammonia levels. Individuals with partial enzyme deficiency may present later in life, typically following an acute illness or other catabolic stressor. Symptoms may be less severe and may appear as episodes of psychosis, lethargy, cyclical vomiting, and behavioral abnormalities. Patients with impaired ornithine metabolism due to ornithine aminotransferase deficiency may present with childhood onset myopia progressing to vision loss in the 4th to 6th decades of life. Patients may or may not have accompanying hyperammonemia but display marked elevations in plasma ornithine.
All the UCD are inherited as autosomal recessive disorders, with the exception of OTC deficiency, which is X-linked. UCD may be suspected with elevated ammonia, normal anion gap, and a normal glucose.
This comprehensive gene panel is a helpful tool to establish a diagnosis for patients with suggestive clinical and biochemical features given the broad clinical spectrum and genetic heterogeneity of UCD. Molecular genetic testing can help to distinguish among the conditions and allows for diagnostic confirmation.
A combination of biochemical tests including quantitative plasma amino acids (AAQP / Amino Acids, Quantitative, Plasma) and urinary orotic acid (OROT / Orotic Acid, Random, Urine) are recommended as the first-tier test to assess patients for UCD.
Acute treatment for UCD consists of dialysis and administration of nitrogen scavenger drugs to reduce ammonia concentration. Chronic management typically involves restriction of dietary protein with essential amino acid supplementation. More recently, liver transplantation has been used with success in treating some patients.
Reference Values
An interpretive report will be provided.
Interpretation
All detected alterations are evaluated according to American College of Medical Genetics and Genomics recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.
Clinical Reference
1. Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405-424
2. Brusilow SW, Horwich AL. Urea cycle enzymes. In: Valle D, Antonarakis S, Ballabio A, Beaudet A, Mitchell GA. eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill Education; 2019. Accessed March 8, 2024. Available at https://ommbid.mhmedical.com/content.aspx?sectionid=225084071&bookid=2709&Resultclick=2
3. Haberle J, Burlina A, Chakrapani A, et al. Suggested guidelines for diagnosis and management of urea cycle disorders: First revision. J Inherit Metab Dis. 2019;1-39. doi:10.1002/jimd.12100
4. Valle D, Simell O. The hyperornithinemias. In: Valle D, Antonarakis S, Ballabio A, Beaudet A, Mitchell GA. eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill Education; 2019. Accessed March 8, 2024. Available at https://ommbid.mhmedical.com/content.aspx?sectionid=225083672&bookid=2709&Resultclick=2
5. Foshci FG, Morelli MC, Savini S, et al. Urea cycle disorders: A case report of a successful liver transplant and a literature review. World J Gastroenterol. 2015;21(13):4063-4068
6. Ah Mew N, Simpson KL, Gropman AL, et al. Urea cycle disorders overview. In: Adam MP, Everman DB, Mirzaa GM, et al. eds. GeneReviews [Internet]. University of Washington, Seattle; 2003. Updated June 22, 2017. Accessed March 8, 2024. Available at www.ncbi.nlm.nih.gov/books/NBK1217/
Test Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.CPT Code Information
81443
88233-Tissue culture, skin, solid tissue biopsy (if appropriate)
88240-Cryopreservation (if appropriate)
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| UCDP | Urea Cycle Disorders Gene Panel | 105267-9 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 608644 | Test Description | 62364-5 |
| 608645 | Specimen | 31208-2 |
| 608646 | Source | 31208-2 |
| 608647 | Result Summary | 50397-9 |
| 608648 | Result | 82939-0 |
| 608649 | Interpretation | 69047-9 |
| 608650 | Resources | 99622-3 |
| 608651 | Additional Information | 48767-8 |
| 608652 | Method | 85069-3 |
| 608653 | Genes Analyzed | 48018-6 |
| 608654 | Disclaimer | 62364-5 |
| 608655 | Released By | 18771-6 |
Day(s) Performed
Varies
Report Available
21 to 35 daysTesting Algorithm
For skin biopsy and cultured fibroblast specimens, fibroblast culture will be added at an additional charge. If viable cells are not obtained, the client will be notified.
Reflex Tests
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| CULFB | Fibroblast Culture for Genetic Test | Yes | No |
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